The production of hybridomas by cell fusion is an increasingly important aspect of both research and clinical protocols. Almost all fusions are done with techniques which have low absolute fusion efficiency (typically 1 in 100,000, require large numbers of cells (typically a billion) and are partially toxic to the cells. We have recently conducted preliminary research on a new approach, the Electronic Cell Fusion Technique. This technique uses a microchamber with electrodes to cause the cells to be held by pairs in contact to each other. An electronic impulse is then used to puncture the membrane at the point of contact which immediately induces the onset of fusion. This method has the potential to overcome all of the limitations mentioned above and make possible the successful fusion of a wide variety of cell partners not previously addressable. The resulting hybridomas will be of use in many areas including HLA typing, antitoxin production and basic research. Biofusion, Inc. in collaboration with the Massachussets General Hospital proposes to do the research necessary to develop a reliable and practical electronic cell fusion apparatus along with a protocol suitable for the general problem of creating a wide variety of hybridomas. In addition, as a specific practical target, as well as a vehicle for proof of concept, we propose to make specific human antibodies for HLA typing. In Phase I we will focus on research to demonstrate both the potential strengths and the present limitations of the Electronic Cell Fusion Technique. In Phase II, we will perfect the technique and strive to make the human HLA antibodies. The potential commercial market for monoclonal antibodies is extremely large. The ability of the Electronic Cell Fusion Technique to fuse very small numbers of cells with high efficiency should allow Biofusion, Inc. to produce a unique line of products, especially in the areas of HLA typing and antitoxins. By teaming with a large company for Phase III of the program, the results of a successful research program will be of both scientific and commercial importance in the medical field.